We propose to carry out a rapid genome-wide search for new mitogens and survival factors for stem and precursor cells of the CNS, potentially doubling or more the number of known CNS mitogenic and survival factors over the course of two years. To do this, a novel protein expression technology, called Random Activated Gene Expression (RAGE), will be used. RAGE libraries containing as few as 5 million individual clones have been shown to be capable of expressing protein from the vast majority of human genes. By combining the RAGE protein expression libraries with the cellular assays described herein, mitogenic and survival factors can be rapidly identified, cloned, and over-expressed to levels suitable for commercialization (e.g., 250 mg/liter). In addition to potential direct medical and therapeutic benefits, the discovery of new proteins with activities in promoting cell survival and division has considerable benefits on biological research in general. Even the limited number of growth factors available has provided a central foundation for the nascent field of stem cell biology in the CNS. Identifying proteins that further enable regulation of these populations will provide tools that may greatly extend our ability to achieve such important goals as repair of CNS damage.
Novel genes and proteins discovered in the present program have several commercial applications. First, novel genes and/or proteins will be made available to the research community as a research product. This will occur most likely by licensing research rights to an established company specializing in the sale and distribution of research reagents. Second, novel genes and proteins will be investigated as potential therapeutic agents in established animal models of human disease. Genes and proteins with demonstrated activity will be further evaluated as drug candidates, and potentially developed clinically. Typically, an established pharmaceutical partner would be identified to facilitate development and commercialization of the drug candidate.
